Comparison of solithromycin with erythromycin in Enterococcus faecalis and Enterococcus faecium from China: antibacterial activity, clonality, resistance mechanism, and inhibition of biofilm formation


Solithromycin (SOL), a fourth-generation macrolide and ketolide, has been reported to have robust antibacterial activity against a wide spectrum of Gram-positive bacteria. However, the impact of SOL on planktonic growth and biofilm formation of clinical enterococcus isolates remains unclear. In this study, 276 Enterococcus faecalis isolates and 122 Enterococcus faecium were retrospectively collected from a tertiary hospital from China. SOL against clinical isolates of enterococci from China were evaluated the antimicrobial activity in comparison with erythromycin, and explore its relationship with the clonality, virulence genes and resistance mechanism of these isolates. Our data showed that the MICs of SOL against clinical E. faecalis and E. faecium isolates from China were ≤4 and ≤8 mg l−1, respectively. ST16 and ST179 were regarded as the risk factor to SOL resistance in E. faecalis. SOL could inhibit but not eradicate the biofilm formation of E. faecalis. The bactericidal effects of SOL against E. faecalis and E. faecium were demonstrated to be similar to linezolid and vancomycin using time-kill assays. In conclusion, SOL showed significantly enhanced antibacterial activity against clinical isolates of E. faecalis and E. faecium from China in comparison to erythromycin. Furthermore, SOL could inhibit the biofilm formation of E. faecalis and have the similar bactericidal ability as linezolid and vancomycin against both E. faecalis and E. faecium.

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  1. 1.

    Akpaka PE, Kissoon S, Wilson C, et al. Molecular characterization of vancomycin-resistant Enterococcus faecium isolates from Bermuda. PLoS ONE. 2017;12:e0171317.

    Article  Google Scholar 

  2. 2.

    Ball TA, Monte DF, Aidara-Kane A, et al. Phenotypic and genotypic characterization of Escherichia coli and Salmonella enterica from dairy cattle farms in the Wakiso District, Uganda: a cross-sectional study. Foodborne Pathog Dis. 2019;16:54–9.

    CAS  Article  Google Scholar 

  3. 3.

    Sievert DM, Ricks P, Edwards JR, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010. Infect Control Hosp Epidemiol. 2013;34:1–14.

    Article  Google Scholar 

  4. 4.

    Hidron AI, Edwards JR, Patel J, et al. NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007. Infect Control Hosp Epidemiol. 2008;29:996–1011.

    Article  Google Scholar 

  5. 5.

    Ike Y. Pathogenicity of enterococci. Nihon SaikingakuZasshi. 2017;72:189–211.

    CAS  Article  Google Scholar 

  6. 6.

    Al-Zubidi M, Widziolek M, Court EK, et al. Identification of novel bacteriophages with therapeutic potential that target Enterococcus faecalis. Infect Immun. 2019;87:e00512–19.

    CAS  Article  Google Scholar 

  7. 7.

    Niebel M, Thamara PR, Perera M, Shah T, et al. Emergence of linezolid resistance in hepatobiliary infections caused by Enterococcus faecium. Liver Transplant. 2016;22:201–8.

    Article  Google Scholar 

  8. 8.

    Sassi M, Guérin F, Zouari A, et al. Emergence of optrA-mediated linezolid resistance in enterococci from France, 2019. J Antimicrob Chemother. 2019;74:1469–72.

    CAS  Article  Google Scholar 

  9. 9.

    Suay-García B, Pérez-Gracia MT. Future prospects for Neisseria gonorrhoeaetreatment. Antibiotics. 2018;7:49.

    Article  Google Scholar 

  10. 10.

    Salerno SN, Edginton A, Cohen-Wolkowiez M, et al. Development of an Adult physiologically based pharmacokinetic model ofsolithromycin in plasma and epithelial lining fluid. CPT Pharmacomet Syst Pharmacol. 2017;6:814–22.

    CAS  Article  Google Scholar 

  11. 11.

    Fernandes P, Pereira D, Watkins PB, Bertrand D. Differentiating the pharmacodynamics and toxicology of macrolide and ketolide antibiotics. J Med Chem. 2020;63:6462–73.

    CAS  Article  Google Scholar 

  12. 12.

    Okusanya OO, Forrest A, Bhavnani SM, et al. Pharmacokinetic/pharmacodynamic evaluation of solithromycin against Streptococcus pneumoniae using data from a neutropenic murine lung infection model. Antimicrob Agents Chemother. 2019;63:e02606–18.

    CAS  Article  Google Scholar 

  13. 13.

    Gonzalez D, James LP, Al-Uzri A, et al. Population pharmacokinetics and safety of solithromycin following intravenous and oral administration in infants, children, and adolescents. Antimicrob Agents Chemother. 2018;62:e00692–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Keelan JA, Kemp MW, Payne MS, et al. Maternal administration of solithromycin, a new, potent, broad-spectrum fluoroketolide antibiotic, achieves fetal and intra-amniotic antimicrobial protection in a pregnant sheep model. Antimicrob Agents Chemother. 2014;58:447–54.

    Article  Google Scholar 

  15. 15.

    Darpo B, Sager PT, Fernandes P, et al. Solithromycin, a novel macrolide, does not prolong cardiac repolarization: a randomized, three-way cross over study in healthy subjects. J Antimicrob Chemother. 2017;72:515–21.

    CAS  Article  Google Scholar 

  16. 16.

    Li Y, Petrova OE, Su S, et al. BdlA, DipA and induced dispersion contribute to acute virulence and chronic persistence of Pseudomonas aeruginosa. PLoS Pathog. 2014;10:e1004168.

    Article  Google Scholar 

  17. 17.

    Beceiro A, Tomás M, Bou G. Antimicrobial resistance and virulence: a successful or deleterious association in the bacterial world? Clin Microbiol Rev. 2013;26:185–230.

    CAS  Article  Google Scholar 

  18. 18.

    Golob M, Pate M, Kušar D, et al. Antimicrobial resistance and virulence genes in Enterococcus faecium and Enterococcus faecalis from humans and retail red meat. Biomed Res Int. 2019;2019:2815279.

    Article  Google Scholar 

  19. 19.

    Arredondo-Alonso S, Top J, McNally A, et al. Plasmids shaped the recent emergence of the major nosocomial pathogen Enterococcus faecium. mBio. 2020;11:e03284–19.

    CAS  Article  Google Scholar 

  20. 20.

    Golińska E, Tomusiak A, Gosiewski T, et al. Virulence factors of Enterococcus strains isolated from patients with inflammatory bowel disease. World J Gastroenterol. 2013;19:3562–72.

    Article  Google Scholar 

  21. 21.

    Lee K, Lee KM, Kim D, Yoon SS. Molecular determinants of the thickened matrix in a dual-species pseudomonas aeruginosa and Enterococcus faecalis biofilm. Appl Environ Microbiol. 2017;83:e01182–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Ahmed SAKS, Rudden M, Smyth TJ, Dooley JSG, Marchant R, Banat IM. Natural quorum sensing inhibitors effectively downregulate gene expression of Pseudomonas aeruginosa virulence factors. Appl Microbiol Biotechnol. 2019;103:3521–35.

    CAS  Article  Google Scholar 

  23. 23.

    Lin Z, Pu Z, Xu G, et al. Omadacycline efficacy against Enterococcus faecalis isolated in China: in vitro activity, Heteroresistance, and Resistance Mechanisms. Antimicrob Agents Chemother. 2020;64:e02097–19.

    CAS  Article  Google Scholar 

  24. 24.

    Bai B, Hu K, Li H, et al. Effect of tedizolid on clinical Enterococcus isolates: in vitro activity, distribution of virulence factor, resistance genes and multilocus sequence typing. FEMS Microbiol Lett. 2018;365.

  25. 25.

    Yao W, Xu G, Bai B, et al. In vitro-induced erythromycin resistance facilitates cross-resistance to the novel fluoroketolide, solithromycin, in Staphylococcus aureus. FEMS Microbiol Lett. 2018;365.

  26. 26.

    Yao W, Xu G, Li D, et al. Staphylococcus aureus with an erm-mediated constitutive macrolide-lincosamide-streptogramin B resistance phenotype has reduced susceptibility to the new ketolide, solithromycin. BMC Infect Dis. 2019;19:175.

    Article  Google Scholar 

  27. 27.

    Say Coskun US. Investigation of the relationship between virulence factors and antibiotic resistance of Enterococci isolates. Cell Mol Biol (Noisy-le-Gd). 2019;65:14–7.

    Article  Google Scholar 

  28. 28.

    Zheng JX, Wu Y, Lin ZW, et al. Characteristics of and virulence factors associated with biofilm formation in clinical Enterococcus faecalis isolates in China. Front Microbiol. 2017;8:2338.

    Article  Google Scholar 

  29. 29.

    Jung S, Park OJ, Kim AR, et al. Lipoteichoic acids of lactobacilli inhibit Enterococcus faecalis biofilm formation and disrupt the preformed biofilm. J Microbiol. 2019;57:310–5.

    CAS  Article  Google Scholar 

  30. 30.

    Zheng JX, Tu HP, Sun X, et al. In vitro activities of telithromycin against Staphylococcus aureus biofilms compared with azithromycin, clindamycin, vancomycin and daptomycin. J Med Microbiol. 2020;69:120–31.

    CAS  Article  Google Scholar 

  31. 31.

    Lorenzo MP, Kidd JM, Jenkins SG, Nicolau DP, Housman ST. In vitro activity of ampicillin and ceftriaxone against ampicillin-susceptible Enterococcus faecium. J Antimicrob Chemother. 2019;74:2269–73.

    CAS  Article  Google Scholar 

  32. 32.

    Ya-Han L, Yi-Hua C, Kuan-Jen C, et al. Infectious sources, prognostic factors, and visual outcomes of endogenous klebsiella pneumoniae endophthalmitis. Ophthalmol Retina. 2018;2:771–8.

    Article  Google Scholar 

  33. 33.

    Kato H, Yamagishi Y, Hagihara M, et al. Antimicrobial activity of solithromycin and levofloxacin against a murine pneumonia mixed-infection model caused by Streptococcus pneumoniae and anaerobic bacteria. J Infect Chemother. 2019;25:311–3.

    CAS  Article  Google Scholar 

  34. 34.

    Piccinelli G, Fernandes P, Bonfanti C, Caccuri F, Caruso A, De, Francesco MA. In vitro activity of solithromycin against erythromycin-resistant Streptococcus agalactiae. Antimicrob Agents Chemother. 2014;58:1693–8.

    Article  Google Scholar 

  35. 35.

    Mallegol J, Fernandes P, Melano RG, Guyard C. Antimicrobial activity of solithromycin against clinical isolates of Legionella pneumophila serogroup 1. Antimicrob Agents Chemother. 2014;58:909–15.

    Article  Google Scholar 

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This work was supported by grants from Science, Technology and Innovation Commission of Shenzhen Municipality of key funds (JCYJ20180508162403996) and basic research funds (JCYJ20180302144345028; JCYJ20180302144431923, JCYJ20180302144721183, JCYJ20180302144340004); Shenzhen Key Medical Discipline Construction Funds (No. SZXK06162); San Ming Project of Medicine in Shenzhen; the Shenzhen Nanshan District Scientific Research Program of the People’s Republic of China (Nos. 2019032, 2019001, 2019004, 2019005, 2019027, and 2018064) and provincial medical funds of Guangdong (Nos. B2017019, 2018116164215307, and A2018163).

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ZY and ZW participated in the design of the study and revised the paper. GX and QD extracted DNA, YW, YX, ZW, and JZ performed PCR amplification and other experiments.

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Correspondence to Zewen Wen or Zhijian Yu.

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This study was approved by the Ethics Committee of Shenzhen Nanshan people’s Hospital, the 6th Affiliated Hospital of Shenzhen University Health Science Center. For this type of study, formal consent is not required.

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Wang, Y., Xiong, Y., Wang, Z. et al. Comparison of solithromycin with erythromycin in Enterococcus faecalis and Enterococcus faecium from China: antibacterial activity, clonality, resistance mechanism, and inhibition of biofilm formation. J Antibiot (2020).

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